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From ideas to innovative Biotech Products
Bio-Engineered Materials
Bio-Engineered Materials
Bio-Engineered Materials
The RFA “Health and Performance” consists of 5 Research Modules one of which is “Bio-Engineered
Materials”.
Biotechnology plays an important role in research on materials in the context of life sciences. It
allows the synthesis, optimization and functionalization of (macro) molecules that can be used to
solve health and performance related problems. Empa uses this technology to develop new
biocatalysts for sustainable chemical processes. Microbiological and (bio)chemical procedures are
applied to synthesize bio-based and bio-degradable polymers such as polyhydroxyalkanoate (PHA)
bio-polyesters. Biopolymers are further modified and functionalized, or are blended with suitable
additives and processed using various techniques to enable novel applications through “green”
materials.
Contact: Linda Thöny-Meyer ([email protected])
Biopolymers
� We apply the principles of modern macromolecular engineering to the preparation of biocompatible
and biodegradable polymer-based materials with well-defined 2D and 3D arrangements for custom-
made applications.
� By precisely controlling the polymers’ average molecular weights, molecular weight distribution,
functionality, composition, and topology, we are able to finely tune the properties of the final material
and thus to meet the specific needs of our academic and industrial research partners.
� Molecules from renewable resources are employed whenever possible. These include: enzymes as
catalysts; plant oils, amino acid and sugar derivatives as monomers; water as solvent; biological polymers
such as PHAs, proteins, etc. as building blocks; hydroxyapatite, cellulose etc. as fillers.
Contact: Fabio di Lena ([email protected], Tel: 058 765 7674)
Isolated and purified PHAs Biodegradable flipflops
Biopolymers - Polymer therapeutics
We design and prepare new macromolecular architectures functioning as inert drug delivery systems or as
bioactive pharmaceuticals in their own right.
Polymer matrices (hydrogels, fibers, foams etc.), with or without the ability to release bioactive molecules,
polymer–drug and polymer–protein conjugates, polymer complexes (polyplexes) for DNA/RNA delivery, and
polymer assemblies (micelles, vesicles, etc.) as encapsulating agents are typical examples of the first class of
compounds.
Polymer sequestrants to remove ions, toxins, etc. from the body, polymers with hemostatic properties, as well as
polymers acting as multivalent ligands for activating given cellular responses or inhibiting the binding of
pathogens are examples of the second class of compounds.
Examples of polymer delivery systems for therapeutic applications
Biopolymers - Microencapsulation
In addition to drugs, micro- and nano-sized polymer assemblies can be used as convenient encapsulating
agents for other active ingredients such as agrochemicals, food additives, flavors and fragrances. Our research
moves also in this direction.
The key advantages that these polymeric systems offer include: (i) sustained delivery, i.e., release over extended
periods of time; (ii) shielding of sensitive ingredients from the surrounding environment; (iii) isolation of the
unpleasant taste or odor of some additives; and (iv) protection of particularly volatile compounds.
Many drugs, agrochemicals, food additives, flavors and fragrances share two important features: (i) they are
“small”, (usually) hydrophobic organic molecules; and (ii) they come into contact with living organisms and the
environment. Hence, several delivery systems originally designed for drugs can be adapted to encapsulate and
release, in a controlled way, these other molecules as well.
Agrochemicals Microcapsules
Biopolymers - Bionanocomposites
We make use of nano-sized fillers based on montmorillonite and hydroxyapatite (inorganic), cellulose (organic)
or polymer particles (organic/inorganic) to improve the chemical (resistance, degradability, etc.) and/or the
physical (mechanical, thermal, barrier, etc.) properties of biopolymers. To this end, not only we use the fillers as
received by the providers but also we modify their surface via polymer grafting in order to (i) improve the
interaction with the matrix, (ii) optimize the dispersion within the matrix, and (iii) minimize their aggregation.
The processing tools we employ include:
� 16 mm co-rotating twin screw extruder (0.1-1 kg/h) with volumetric feeder;
� Several square dies (0.5-2mm x 20 mm); 3 mm strand die;
� Gravimetric feeder (5-50 g/h);
� Compression molder;
� Roll mill
Layered nanocomposites
Microbial Engineering
Microbial engineering uses the capabilities of microorganisms to produce useful biological materials, especially,
biopolymers and recombinant proteins. We are active in:
� biosynthesis and downstream processing of proteins, biomolecules and biopolymers;
� applying different culture technologies and efficient product recovery steps to generate safe and
reproducible materials at reasonable cost;
� investigation of interactions between microbes and material surfaces.
Contact: [email protected], Tel: 058 765 7688.
Microbial Engineering Biopolymer production
Polyhydroxyalkanoates (PHAs) are produced by bacteria and featured with biodegradability and
biocompatibility. PHAs are difficult to produce using synthetic chemistry due to their high molecular weight
and/or chirality. We focus on:
� production of tailor-made PHAs with or without functional side-chains;
� synthesis of PHAs from cheap carbon sources such as xylose, a major waste product of the paper
industry;
� manufacturing PHAs as coatings of metallic bone implants and other medical devices, and as
components of artificial tendon;
� production of enantiomerically pure 3-hydroxycarboxylic acids from PHA
We attempt to develop a biotechnological approach for PHA production which offers sustainability from both
environmental and economic aspects.
Conversion of polymer to monomers PHA producing bacteria
Microbial Engineering Recombinant protein production
Recombinant protein production in E. coli tends to be more robust, faster and cheaper than in mammalian
systems. In our laboratory, we work on:
� production of glycosylated proteins in recombinant E. coli at a larger scale. By process optimization,
volumetric glycoconjugate yield in bioreactors could be increased 50-fold compared to shake flasks;
� production of a novel tyrosinase. By process optimization, the volumetric yield of tyrosinase in
bioreactors was increased 16-fold compared to shake flasks.
Parallel bioreactor system Overproduced green fluorescent protein
Microbial Engineering Interactions of microbes with surfaces
Microbial adhesion and growth on material surfaces have serious economic, environmental and health
implications such as biofouling, biocorrosion and infections. We investigate:
� Textile: antimicrobial / anti-adhesion effects of textile coatings;
� Medicals: antifouling activity of silver coated materials, antibacterial effect of new products in wound
management, cleaning efficiency of new formulations of detergents;
� Household: test systems to measure biofilm removal in washing machines;
� Environment: waste water analyses, antibacterial coatings in the area of plant protection.
Biofilm stained with Concavalin A Classical antimicrobial test Biofilm formation in the
bioreactor
Biocatalysis
� is a green chemical technology;
� involves the use of enzymes for chemical reactions in diverse synthetic and technological applications;
� works at moderate reaction conditions, and enzymes can be optimized in the laboratory for specific
processes by enzyme engineering.
Future trends in enzyme technology target the functionalization of natural and synthetic (bio)polymers, waste
water purification and the fabrication of hybrid materials for energy production.
Contact: [email protected], Tel.: 058 765 7868.
Biocatalysis Laccases
� are multi-copper oxidases that catalyse the one electron oxidation of a broad range of compounds
including substituted phenols, arylamines and aromatic thiols;
� enable controlled, selective and catalytic oxidation reactions;
� are well-suited for technical processes due to their broad substrate range, high specific activity, stability
and due to fact that they only need oxygen as co-substrate
Potential applications include organic synthesis, bleaching of textiles and paper or production of wood
compound materials.
At Empa we develop novel bacterial laccases for industrial applications using technologies such as directed
evolution.
Model of a bacterial laccase active site Purified Laccase Screening patterns for functional laccases
Biocatalysis Directed evolution
Enzymes can be optimized in the laboratory to fulfill specific technical needs such as thermostability, solvent
tolerance and high activity. Therefore, the principles of biological evolution are applied to specific target genes.
State-of-the art molecular biology tools are used to generate genetic diversity and high throughput screening
methods for the selection of improved variants. Empa contributes to projects with industrial partners by:
� developing novel screening methods for enzyme activity in 96-well format;
� designing and constructing random and semi-random mutant gene libraries;
� discovering glycosyl transferase and oxidoreductase variants with increased activity.
improved
enzyme
variant
library
mutagenesis
screening
enzyme
Principle of directed evolution (left) and 96-well micro plate for screening of enzyme variants (right)
Biocatalysis Tyrosinases
Tyrosinases are copper containing oxidases that convert phenolic substrates. There are many applications for
this class of enzymes in the fields of biocatalysis, biomaterials and biosensors, including:
� the degradation of phenolic waste products;
� bio-sensing of phenolic compounds;
� covalent cross-linking of tyrosyl side chains in polypeptides with nucleophilic groups in polypeptides or
other polymers, for example with amino groups in chitosan;
� functionalization of polymeric materials or the gentle formation of stable, active enzyme aggregates.
Model of a bacterial tyrosinase and mechanism of tyrosinase catalyzed protein crosslinking
Biocatalysis Biosensor Fabrication
Certain oxidoreductases can be used for the development of novel biosensors.
In electrochemical biosensors these enzymes are immobilized by different means onto conducting surfaces. The
specific reaction with the molecule of interest consumes or releases electrons directly or indirectly, causing an
electrical signal. This allows the selective, qualitative or quantitative detection of specific chemicals in a mixture
of substances.
We are currently developing and engineering various oxidoreductases (e.g. P450 enzymes) for the specific
detection of natural metabolites for the use in microfabricated sensor devices.
Architecture of a microfabricated electrochemical biosensor
Biocatalysis Enzymatic surface functionalization
Enzymes such as laccase or tyrosinase can be used for surface functionalization of inorganic and organic (bio)
materials by
� modifying surface exposed functional groups, e.g. for increased hydrophilicity;
� activating and coupling small molecules to the surface e.g. for antimicrobial effects;
� in situ polymerizing and crosslinking biopolymers for biocompatible coatings;
� site-specific cross-linking of proteins, peptides and biopolymers to surfaces for obtaining novel bio-
hybrid materials.
Lyophilized bacterial laccase Principle of laccase-catalysed iodination for the protection of wood
against microorganisms
Contact: [email protected], Tel.: 058 765 7798
Biocatalysis Protein Immobilization
Our aim is to fabricate functional protein-modified surfaces.
� By modifying surfaces with proteins and peptides we produce novel hybrid materials with unique
properties that are useful for a wide range of applications, ranging from organic synthesis over
biosensing to biomimetic photoelectrochemical cells.
� We employ various chemical and enzymatic immobilization techniques to anchor the selected target
molecules on the surface.
Protein immobilization techniques Green fluorescent protein immobilized on polystyrene
beads by sortase
Biocatalysis Biohybrid Materials
Enzymatic protein immobilization can be used in combination with organic polymers resulting in
semiconductor surfaces functionalized in a well ordered manner. In this way the performance and stability
of solar cells for electrochemical water splitting using Solar light can be optimized in environmentally
friendly conditions.
Self-organized protein-biopolymer fractal structure on a photo anode
Mycowood
Contact: [email protected]
Improved acoustic properties for violins
The method allows improving the acoustic properties of resonance wood in times where it is becoming
increasingly difficult to find superior resonance wood due to the impact of global warming. The main objective
of this interdisciplinary project is the successful up scaling of our biotechnological process of fungal
modification by defining standardized conditions to achieve reproducible results, and by better defining the
notion of “resonance wood quality”. If the outcome of the project is successful, in the future, every talented
musician will be able to afford a violin with the same tonal quality as an expensive Stradivarius.
Fungal treated Opus 58 at a trade exhibition in Basle
Mycowood Enhanced permeability of Norway spruce wood by fungal modification
Aspiration of bordered pits in Norway spruce wood is the main reason why the treatability with preservatives is
greatly inhibited for increasing the durability against micro-organisms. If this restriction could be overcome
wood could be treated more effectively. For this purpose Norway spruce wood is exposed to the white-rot
fungus Physisporinus vitreus that selectively degrades the pit membranes, without altering the mechanical
properties of wood. At present we are undertaking studies to improve the permeability of water-borne wood
preservatives or hydrophobic substances applied by brushing, dipping and impregnation.
Heartwood specimens of Norway spruce (top) and White Fir (bottom) impregnated with a 0.1 % aqueous solution of the dye
Neolan Glaucin E-A. A significant increase in the uptake of the dye (in kg/m3) is apparent in fungal treated wood specimens.